The microsomal monooxygenase system, consisting of the flavoprotein, NADPH-cytochrome P-450 reductase, and a family of hemeproteins, cytochromes P-450, is involved in the initial oxidative metabolism of xenobiotics including therapeutic drugs, polycyclic aromatic hydrocarbons, and pesticides as well as a variety of endogenous compounds such as steroids. Over 250 agents have been shown to induce this enzyme system both by increasing the content of these enzymes present in the endoplasmic reticulum and in altering the rate at which substrates are metabolized. Since alteration in the rate or substract specificity of the reactions catalyzed by these enzymes can have dramatic effects on the turnover of therapeutic drugs, the activation of carcinogens, and the levels of steroid hormones, the objective of the proposed work is an investigation of the influence of two chlorinated insecticides, Kepone and Mirex, on the activities of the microsomal monooxygenase system in the liver, the primary site of drug metabolism, as well as other tissues. A study of the effects of these agents assumes increased importance because of the persistence of these compounds in the environment and the accidental exposure of the human population to these agents, which has resulted in disabling illness.